title: Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis.
abstract: We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2 concentrations (FIO2) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 x 10(10) colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing FIO2 (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial PO2 [-0.3 +/- 0.6, 3 +/- 1, 13 +/- 4, 10 +/- 9 (mean +/- SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 +/- 0.3, 4 +/- 2, -8 +/- 7, -10 +/- 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean PO2 with increasing FIO2 (2 +/- 1, -5 +/- 3, -2 +/- 3, and -12 +/- 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 +/- 0.04, 2 +/- 2, 1 +/- 3, 11 +/- 5 Torr; P < 0.05 compared with infected animals). In normal and infected animals alike, only at FIO2 < or = 0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonary artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high FIO2 and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.
authors.affiliation: Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Quezado
authors.forename: C
authors.initials: C
authors.lastname: Natanson
authors.forename: W
authors.initials: W
authors.lastname: Karzai
authors.forename: R L
authors.initials: RL
authors.lastname: Danner
authors.forename: C A
authors.initials: CA
authors.lastname: Koev
authors.forename: Y
authors.initials: Y
authors.lastname: Fitz
authors.forename: D P
authors.initials: DP
authors.lastname: Dolan
authors.forename: S
authors.initials: S
authors.lastname: Richmond
authors.forename: S M
authors.initials: SM
authors.lastname: Banks
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.forename: P Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D004285:Dogs; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011014:Pneumonia / Q000382:microbiology / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide